As a conventional method for preparing a 2-(5-halogeno-2-nitrophenyl)-2-substituted acetic acid ester compound from 2,4-dihalogenonitrobenzene compound, it has been known a method of synthesizing dimethyl 2-(5-halogeno-2-nitrophenyl)malonate by reacting dimethyl malonate with 2,4-dihalogenonitrobenzene in the presence of sodium hydride in dimethyl sulfoxide (Synthesis, 1993, 51). However, according to this method, complicated operations are required since sodium hydride having highly ignitable property is used and the reaction generates a hydrogen gas, so that it has problems as an industrial production process.
Also, as a process for producing 5-fluorooxindole from 2-(5-fluoro-2-nitrophenyl)malonic acid diester which is a kind of the above-mentioned 2-(5-halogeno-2-nitrophenyl)-2-substituted acetic acid ester, it has been described in Synthesis, 1993, 51, a process for producing 5-fluorooxindole by reacting lithium chloride with dimethyl 2-(5-fluoro-2-nitrophenyl)malonate in a mixed solvent of water and dimethyl sulfoxide to once form methyl 5-fluoro-2-nitrophenylacetate, and then, reducing the resulting compound in acetic acid in the presence of iron and cyclizing the resulting compound. However, according to this process, there are problems that the reaction system is complicated and a total yield of the objective compound is as low as 49%.
An object of the present invention is to solve the above-mentioned problems and to provide an industrially suitable process for preparing 5-fluorooxindole from an easily available 2-(5-fluoro-2-nitrophenyl)malonic acid diester with a simple and easy method and a high yield.
A further object of the present invention is to solve the above-mentioned problems and to provide an industrially suitable process for preparing a 2-(5-halogeno-2-nitrophenyl)malonic acid diester compound from a 2,4-dihalogenonitrobenzene compound with a simple and easy method.
A still further object of the present invention is to provide a novel 5-fluorooxindole-3-carboxylic acid ester and a 2-(5-halogeno-2-nitrophenyl)-2-substituted acetic acid ester compound which are useful as synthetic intermediates of the above-mentioned preparation processes.